SAT-292 Rare But Real: Navigating The Journey Of Immunotherapy-induced Hypoparathyroidism

Abstract Disclosure: A. Nepal: None. N. Kumari: None. P. Khatiwada: None. Introduction: Immune checkpoint inhibitors (ICI) are breakthrough advancement in treatment of cancers. But they present with many immune-related adverse events: irAE, thyroid disorders, T1DM and hypophysitis being more common, and hypoparathyroidism, adrenalitis, and central DI being rare. There are only 4 reported cases of ICI-induced hypoparathyroidism. We report a very rare case of combined hypoparathyroidism and hypothyroidism induced by ICI: Druvalumab (a PD-L1 inhibitor) followed by pembrolizumab (PD-1 inhibitor) and its management. Case presentation: 73-year-old male with squamous cell Carcinoma of lung, treated with druvalumab(5/2022-3/2023, 12 cycles) followed by pemrolizumab every 21 days, already on increasing doses of thyroxine due to ICI induced hypothyroidism started developing asymptomatic hypocalcemia (intermittent hypocalcemia one month after start of druvalumab and persistant hypocalcemia 3 months after starting druvalumab). Hypocalcemia progressively worsened with symptoms of perioral numbness, digital tingling and parasthesias, with nadir total calcium of 6.1 mg/dl, ionized calcium of 0.67 mmol/l, PTH of 4 pg/ml). He did not have a history of neck surgery, autoimmune conditions or radiation to the neck. Results: Calcium of 6.1mg/dl and iCal 0.67, 25-hydroxyvitamin D 43, PTH 4 pg/ml. The patient was treated with parenteral calcium followed by oral calcium, calcitriol, and vitamin D3. He was followed by Endocrinology with close monitoring of calcium, PTH levels, and other electrolytes. He responded well to calcium, calcitriol, and vitamin D supplementation, with maintenance of normal calcium levels with minor fluctuation. Unfortunately, the patient eventually succumbed to recurrent squamous cell carcinoma with widespread metastasis. Discussion: The chronology with initiation of immunotherapy and subsequent endocrinopathies was highly suggestive of ICI-induced hypothyroidism and hypoparathyroidism. ICI-induced hypoparathyroidism is considered a rare immune-related adverse event, with there being only 4 case reports available to the best of our knowledge. Pathophysiology is not known, with some authors suggesting T cell infiltration of parathyroid glands, parathyroid inflammation, or CaSR activating antibodies as some possibilities. Measurement of antibodies activating CaSR is not widely available, which makes ICI-induced hypoparathyroidism a clinical diagnosis. More data is needed on the diagnosis and management of this condition. Conclusion: Hypoparathyroidism is a rare but real immune-related adverse event of ICI. Calcium levels should be periodically monitored in all patients on ICI. Treating physicians should be aware of this possibility and have a lower threshold of referral to Endocrinology when ICI-induced endocrinopathies occur. Presentation: Saturday, July 12, 2025